Radix scutellariae, first published in Shen Nong's Herbal Classic, is the dry root of Scutellaria baicalensis Georgi, Labiatae family, effective in clearing away pathogenic heat and dampness, purging intense fire and detoxicating, facilitating hemostasis and preventing miscarriage. Baicalin is a flavonoid compound with a molecular formula of C21H18O11, which is more than 9% by weight or even up to 20% by weight in radix scutellariae and is one of main active ingredients of radix scutellariae.
Modern pharmacological researches have indicated that baicalin plays a role in eliminating oxygen free radicals, antiarrhythmia, dilating heart and cerebral vessels, reducing blood pressure and keeping calm, protecting liver and gallbladder and anti-pathogen, and also inhibits tumors such as prostate cancer, cervical cancer, lung cancer, malignant lymphoma, myeloma and liver cancer. Clinically, there have been various preparations such as baicalin tablets and baicalin capsules, which are mainly used for treating acute and chronic hepatitis, cardiovascular diseases and the like.
Magnesium is an element essential for the activities of normal life and metabolism of living organisms. Magnesium affects various biological functions of cells including transport of potassium ions and calcium ions, regulation of cell signaling, energy metabolism, protein and nucleic acid synthesis; activation and inhibition of catalyticase; and regulation of cell cycle, cell proliferation and cell differentiation. Also, magnesium participates in maintaining genomic stability and is associated with oxidative stress and tumorigenesis in the body.
Baicalin is soluble in alkaline solutions such as sodium hydroxide, sodium carbonate and sodium bicarbonate, but it is unstable in alkaline liquor and will gradually turn to dark brown. It is slightly soluble in hot glacial acetic acid, hardly soluble in methanol, ethanol and acetone and insoluble in water, benzene, ether and chloroform. Since baicalin is almost insoluble in water, oral bioavailability of baicalin is low, so that the clinical application of baicalin is greatly limited.
Recently, there are many related reports on the use of new preparation techniques to improve the solubility and bioavailability of baicalin, involving the preparation of baicalin into metal complexes, β-cyclodextrin inclusion compounds, solid dispersions, phospholipid complexes, microparticles, nanoparticles, liposome nanoemulsions, microemulsions, gelatin microspheres, and the like.
As described in Chinese Pharmacopeia under Radix Scutellariae Extract (2015, Part I), baicalin is obtained through water extraction and acid precipitation and purification through alkali-soluble acid precipitation. The commercially available baicalin is generally prepared by this method. Baicalin is found in radix scutellariae as a magnesium salt. This form of baicalin has good water solubility and may be extracted by water dissolution. However, the original structure of the baicalin will be damaged by acid precipitation, resulting in low water solubility, slow adsorption rate and low baicalin bioavailability, as well as reduced baicalin efficacy.
The present invention provides a method for extracting baicalin magnesium from radix scutellariae without changing the original form of baicalin as found in radix scutellariae, and further provides a method for synthesizing baicalin magnesium using the commercially available baicalin as raw material, in a manner that the baicalin is returned to its original form existed in the radix scutellariae. The baicalin magnesium can be used as a substitute for the baicalin. Baicalin magnesium has greatly increased solubility, faster adsorption rate and higher oral bioavailability as compared to the baicalin. The baicalin magnesium can also be easily formulated as a water-soluble injection or a powder injection. Moreover, the compound can also display the synergistic pharmacological actions of baicalin and magnesium ions, thereby enhancing the efficacy.
The present invention is designed on the basis of a large number of experiments and analysis.